2012 update: Our structures of Y. pestis FyuA and pesticin allowed us to engineer a novel phage therapy drug against a Gram-negative pathogen: We solved the structure of FyuA, a TonB-dependent iron transporter required for virulence in bubonic plague, with and without its cognate siderophore, ferric yersiniabactin. At the same time, we determined the structure of a bacteriocin called pesticin that uses FyuA to cross the outer membrane. Once inside the periplasm, pesticin kills the cell by degrading the peptidoglycan layer. From our structure we discovered that the killing domain of pesticin resembles phage T4 lysozyme, so we engineered a hybrid bacterial-phage toxin that contains a bacterial targeting domain (to FyuA) and a phage killing domain. We showed that the hybrid lysine evades the natural protection mechanism of toxin-producing strains and kills all Yersinia strains tested, both in vitro and in vivo (mouse model of bubonic plague). This is the first demonstration of phage therapy for Gram-negative pathogens because until now, no one knew how to transport the toxin across the outer membrane. This work was recently published at PNAS and has received considerable attention, including a Nature Microbiology Reviews Highlight. In our efforts to identify additional virulence factors that might be used for vaccine and or drug design, we completed a structural study of two monomeric autotransporters from pathogenic E. coli and Yersinia. Intimins and invasins are virulence factors produced by pathogenic Gram-negative bacteria. They contain C-terminal extracellular passenger domains that are involved in adhesion to host cells and N-terminal &#946; domains that are embedded in the outer membrane. We identified the domain boundaries of an E. coli intimin &#946; domain and used this information to solve its structure and the &#946; domain structure of a Y. pseudotuberculosis invasin. Both &#946; domain structures crystallized as monomers and reveal that the previous range of residues assigned to the &#946; domain also includes a protease-resistant domain that is part of the passenger. Additionally, we identified 146 nonredundant representative members of the intimin/invasin family based on the boundaries of the highly conserved intimin and invasin &#946; domains. We then used this set of sequences along with our structural data to find and map the evolutionarily constrained residues within the &#946; domain. This work was recently published in Structure.